CN112533615A

CN112533615A - Hypochlorous acid based eyelid cleaner

Info

Publication number: CN112533615A
Application number: CN201980029518.9A
Authority: CN
Inventors: 小纳特·阿德金斯; 辛西娅·巴勒特; T·梅森; P·萨卡尔
Original assignee: American Okko Vision Co ltd
Current assignee: American Okko Vision Co ltd; Ocusoft Inc
Priority date: 2018-05-02
Filing date: 2019-05-01
Publication date: 2021-03-19
Also published as: KR20210005936A; SG11202010874SA; GB2589225B; GB2589225A; US20190336415A1; CA3099166A1; US11806415B2; US20210369574A1; EP3787641A4; US11090236B2; AU2019262032A1; GB202018968D0; WO2019213266A1; EP3787641A1; JP2021523124A; MX2020011605A; TW202002949A

Abstract

An antimicrobial eyelid cleanser composition comprising: (a) hypohalous acid; (b) one or more surfactants having an HLB value of from 5 to 18; and (c) an aqueous carrier comprising: (i) one or more tonicity adjusting agents; (ii) one or more osmolytes for regulating the osmotic pressure of the composition; and (iii) one or more pH adjusting agents for maintaining the pH of the composition between about 4.5 to about 8.0. The composition may be dispensed in the form of a foam, liquid, spray, mist, gel or lotion. The composition can promote long-term eyelid hygiene by removing excess oil, debris and shed skin, and can relieve ocular inflammation.

Description

Hypochlorous acid based eyelid cleaner

Technical Field

The present invention relates generally to eyelid and skin cleansing compositions, and to methods of making and using such compositions.

Background

Ocular health is directed to the eye and eye-related structures, such as the eyelids. Eyelids are particularly important for overall ocular health because they protect the eyes from hazards (such as approaching objects) or from airborne contaminants (such as pollen, dust particles, or other foreign matter). The eyelids include essential glands: the lacrimal and meibomian glands, which produce a multi-layered tear film that is critical to a healthy eye. When a person blinks, a new tear film forms and tears distribute across the cornea to lubricate the surface of the eye. This blinking action also "flushes" the eye of foreign bodies.

However, the eyelids are subject to certain problems which, although extremely common, are still annoying, especially for contact lens wearers, and can lead to other, more serious complications. One complication is blepharitis. Blepharitis is a common chronic inflammation of the eyelids characterized by a scaly scab on the lid margin. The condition may be caused by bacterial infection and it may originate from allergies or may be associated with seborrhea of the face and scalp. Treatment typically involves cleaning the eyelid periodically to remove excess oil, debris, and shed skin that can be problematic.

Commonly associated with or secondary to blepharitis is a bacterial infection of the skin surface at the margin of the eyelid, known as endophoritis. Other such infections include external hordeolum (commonly known as hordeolum), which is an infection of the tiny oil-secreting meibomian glands along the margins of the eyelids (around the eyelashes). Hordeolum begins as a red tender bump and usually develops completely within three days. Such conditions are associated with pain, redness and tenderness of the eyelid (or lid) margin. Although hordeolum is often recurrent, periodic cleaning of the eyelid margin can minimize such conditions.

The second problem is aragonioma, which is an inflammation of the meibomian glands within the eyelid. Aragonimas usually grow slowly in 2 to 3 weeks, although they usually do not cause pain, they usually require surgical treatment without treatment.

Due to any of the above described problems, as well as other medical complications such as rosacea and seborrhea, proper eyelid hygiene with eyelid cleansers can minimize the severity of the outbreak, or if found early, can prevent such problems altogether. Eyelid cleansers may also be used to cleanse the eyelashes, eyelids, or periocular areas, and may be used as a pre-operative scrub to help reduce the presence of harmful bacteria that may cause infection, inflammation, or even endophthalmitis in a patient.

Disclosure of Invention

Compositions comprising hypochlorous acid and water, along with other eyelid care compositions, have been successfully used to promote long-term eyelid hygiene, as has been described in applicant's U.S. patent No. 9833399. However, applicants have determined that a single isotonic (isotonics)/isotonic pressure (isodesmar) and physiologically compatible antimicrobial formulation is needed that can also provide cleansing effects based on surfactant formulations.

In one embodiment, an eyelid cleanser composition comprises: (a) hypohalous acid; (b) one or more surfactants having an HLB value of from 5 to 18; and (c) an aqueous carrier comprising: (i) one or more tonicity adjusting agents; (ii) one or more osmolality adjusting agents configured to adjust the osmolality of the composition; and (iii) one or more pH modifiers for adjusting the pH of the composition to between about 4.5 to about 8.0. The composition may be dispensed in the form of a foam, liquid, spray (spray), mist (mist), gel or lotion. The composition can promote long-term eyelid hygiene by removing excess oil, debris and shed skin, and can also alleviate ocular inflammation.

In a preferred embodiment, the hypohalous acid is hypochlorous acid. The composition may comprise 10ppm to 1000ppm hypochlorous acid. In certain embodiments, the composition comprises 50ppm to 300ppm hypochlorous acid.

Preferably, the composition has one or more surfactants having an HLB value of from 10 to 18. When the composition includes a surface-active combination, at least the first surfactant has an HLB value of 10 to 18 and the second surfactant has an HLB value of 5 to 10. The one or more surfactants are selected from the group consisting of: nonionic surfactants and amphoteric surfactants. In certain embodiments, the one or more surfactants are selected from the group consisting of: sorbitan, sorbitan monolaurate, polyoxyethylene or polyethylene glycol (PEG) modified molecules (such as PEG-modified surfactants, PEG-modified phospholipids, PEG-modified sugars), amine oxides, block copolymers, and mixtures thereof. The total concentration of the one or more surfactants in the composition is in the range of 0.01% w/w to 20% w/w of the total composition. In certain embodiments, the total concentration of the one or more surfactants in the composition is in the range of 0.01% w/w to 5% w/w.

The composition is physiologically compatible and isotonic/isotonic. The tonicity modifier may be selected from the group consisting of: sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium lactate, potassium lactate, calcium lactate, and mixtures thereof.

The osmolality adjusting agent is configured to adjust the osmolality of the composition from 100mOsm/kg to 500 mOsm/kg. The osmolality adjusting agent may be selected from the group consisting of: sugar, glycerol, propylene glycol and mixtures thereof.

In one or more embodiments, the composition comprises a foam stabilizer. The foam stabilizer can be methyl glucose polyethylene glycol diester and fatty acid.

In one or more embodiments, the composition comprises from 0.01% w/w to 5% w/w of one or more ingredients selected from the group consisting of: propylene glycol, glycerin, liquid polyols, nut oils and derivatives, flower extracts, fruit extracts, sodium alginate, hyaluronic acid, diglycerides, triglycerides, PEG-75 lanolin, mineral oil, silicone oil and mixtures thereof.

In one or more embodiments, the composition comprises from 0.01% w/w to 5% w/w of one or more ingredients selected from the group consisting of: antioxidants, anti-irritants, coolants, viscosity modifiers, and mixtures thereof.

In another embodiment, a kit for maintaining eyelid hygiene consists essentially of an applicator and an eyelid cleanser composition disclosed herein. The applicator may comprise a low-sensitivity nonwoven hydrophilic material.

In yet another embodiment, a kit for maintaining eyelid hygiene consists essentially of an applicator pre-moistened with an effective amount of an eyelid cleanser composition disclosed herein. The applicator may comprise one or more fabric pads, wherein each pad is individually packaged in a sealable package.

In another embodiment, a method for managing eyelid care comprises applying an effective amount of an eyelid cleanser composition disclosed herein to the eyelid and the area surrounding the eyelid. The composition may be left behind or washed away after application.

Detailed Description

As used herein, the terms and phrases "invention," "present invention," and similar terms and phrases are not limiting, and are not intended to limit the present subject matter to any single embodiment, but rather to encompass all possible embodiments described.

As used herein, all weight percentages (wt%) are based on the total wt% of the skin care composition, unless otherwise specified. Further, all composition percentages are based on a total equal to 100 wt% unless otherwise indicated.

The compositions and methods of use thereof may "comprise", "consist essentially of … … (consistency approach of)" or "consist of … … (consistency of)" any of the ingredients or steps disclosed throughout the specification. As used in this specification and one or more claims, the word "comprising" (and any form thereof, such as "comprises" and "comprises)", "having" (and any form thereof, such as "has" and "has)", "including" (and any form thereof, such as "includes" and "includes)", or "containing" (and any form thereof, such as "contains" and "contains)", is inclusive or open-ended and may include the elements of the invention and does not exclude other elements or elements described herein. The use of the words "a" or "an" when used in conjunction with the term "comprising" in the claims and/or the specification can mean "one," but it also conforms to the meaning of "one or more," at least one, "and" one or more. As used herein, "consisting essentially of means that the invention may include ingredients other than those recited in the claims, provided that such additional ingredients do not materially alter the nature and novel characteristics of the claimed invention. Generally, such additives may be absent at all or present only in trace amounts. However, it is possible to include up to about 10% by weight of materials that can materially alter the nature and novel characteristics of the invention, so long as the utility (degree of utility relative) of the composition is maintained.

All ranges recited herein are inclusive of the endpoints (including those reciting a range between two values). Terms such as "about," "generally," "substantially," and the like, are to be understood as modifying a term or value such that it is not an absolute value. Such terms will be defined by the circumstances under which they are modified and the terms as those terms are understood by those skilled in the art. In one non-limiting embodiment, these terms are defined as being within 5%. The term "substantially" and variations thereof are defined as largely but not necessarily wholly what is specified as understood by those of skill in the art, and in one non-limiting embodiment "substantially" means in the range of 0.01% to 5%.

As used herein, the term "effective amount" of a composition refers to an amount sufficient to elicit a desired biological response. As will be appreciated by those skilled in the art, the effective amount of a substance may vary depending on factors such as the desired biological end value, the patient, and the like. The terms effective amount and clinical effect are used interchangeably in the present invention. For example, an effective/clinically effective amount of the composition is an amount that can be used to promote long-term eyelid hygiene while also substantially reducing inflammation and promoting wound healing of the eyelid.

While the specification concludes with claims particularly pointing out and distinctly claiming the invention, it is believed that the present invention will be more fully understood from the following description.

Eyelid cleanser compositions are ophthalmic/ocular compositions that can cleanse the eyelids and eyes and remove excess oil, debris, and shed skin from the eyelids and surrounding areas while reducing inflammation and promoting wound healing. The compositions comprise a hypohalous acid, one or more surfactants, and an aqueous carrier; the one or more surfactants have a hydrophilic-lipophilic balance (HLB) value in the range between 10 and 18, and the aqueous carrier comprises one or more components for adjusting the pH, tonicity, osmotic pressure of the composition.

The "halo" in hypohalous acids is a halogen selected from the group consisting of: chlorine, bromine, iodine and fluorine. Preferably, the halogen is chlorine and the hypohalous acid is hypochlorous acid. The composition comprises at least 10ppm to 1000ppm hypochlorous acid. In certain embodiments, the composition comprises 50ppm to 300ppm hypochlorous acid.

One or more nonionic or amphoteric surfactants may be used in the formulation to achieve the desired foaming and/or cleaning ability. The inclusion of a surfactant will enhance the ability of the composition to dissolve and remove oil, debris, and shed skin. It may be preferred that the surfactant has foaming capability and comprises a nonionic or amphoteric surfactant having an HLB value between 10 and 18. If more than one surfactant is used, at least one surfactant should have an HLB value between 10 and 18, and the other surfactant or surfactants should have an HLB value between 10 and 18 or an HLB value between 5 and 10. Suitable surfactants that may be used include, but are not limited to, sorbitol esters (such as, but not limited to, Span 20 or sorbitan monolaurate, or polyoxyethylene derivatives of sorbitol esters), polyethylene glycol (PEG) modified surfactants (such as, but not limited to, polysorbate 80, Brij 52, PEG-75 lanolin), modified phospholipids, modified sugars (such as, but not limited to, alkyl glycosides, fatty acid glucamides), amine oxides, and/or block copolymers, such as Pluronic (Pluronic 120, Poloxamer 188). The total concentration of surfactant in the final formulation may range from 0.01% w/w to 20% w/w, but more preferably ranges from 0.01% to 5%.

The aqueous carrier may be deionized water or purified water USP. The composition is physiologically compatible and isotonic/isotonic. The aqueous carrier includes one or more components for adjusting tonicity, osmotic pressure and pH as needed. Preferred tonicity adjusting agents include one or more salts such as the chlorides of sodium, potassium, calcium and magnesium, and sodium/potassium/calcium lactates. The osmotic pressure can be adjusted using sugars, glycerol, propylene glycol and similar ingredients. The osmolality of the composition can be adjusted from about 100mOsm/kg to about 500 mOsm/kg. In certain embodiments, the osmolality of the composition is maintained at about 180mOsm/kg to about 400 mOsm/kg. The tonicity modifier may include sugars, glycerin, propylene glycol, mixtures thereof, and other similar ingredients.

Optimally, the pH of the composition is maintained in a pH range between 4.5 and 8.5, or preferably between 5.0 and 7.0. The pH adjustment does not use conventional pH adjusting agents, which can cause eye irritation. For example, in preparing an aqueous carrier, the pH of the composition is adjusted by locking the target pH by adding buffer components (such as phosphate, citrate, tri-salt, and defined ratios of corresponding acids/bases), or by adding increasing amounts of acid or base under agitation until the desired pH is reached when all ingredients have been dissolved/dispersed.

Hypochlorous acid imparts antimicrobial activity to the composition. The antimicrobial activity varies depending on the concentration of hypochlorous acid, the presence of one or more surfactants, and the pH of the composition. Maintaining the pH of the composition will also optimize the hypochlorous acid, the stability of its antimicrobial activity, and reduce negative reactions with the skin or eyelid without washing off after application to the eyelid or skin.

Although optional, foam stabilizers may be added to the composition and may include, but are not limited to, methyl glucose polyethylene glycol diesters and fatty acids. The fatty acid may be selected from the group consisting of: oleic acid, stearic acid, lauric acid, caprylic acid, and capric acid. Preferably, the one or more foam stabilizing agents include PEG-120 methyl glucose dioleate.

The composition may further comprise an additional component in an amount of up to 5% w/w of the composition. These components include one or more humectants, emollients, moisturizers, or lubricants also commonly added to the compositions and generally referred to herein as humectants. Suitable humectants are propylene glycol, glycerin, polyethylene glycol (e.g., PEG 300,400,600), or generally liquid polyols, nut oils and derivatives, flower extracts (such as rose extract), fruit extracts (such as cucumber extract), sodium alginate, hyaluronic acid, medium chain diglycerides, medium chain triglycerides, PEG-75 lanolin, mineral oil, silicone oil, and mixtures thereof.

The composition further comprises up to 5% w/w of one or more optional components including compounds that are antioxidants (such as but not limited to vitamin E and derivatives thereof, green tea extract, vitamin C and derivatives thereof), anti-irritant/smoothing agents (such as but not limited to allantoin, aloe vera, tea tree oil), cooling agents (such as but not limited to sorbitol, xylitol, menthol, thymol) and viscosity modifiers (such as but not limited to carboxymethyl cellulose, hydroxypropyl methyl cellulose, methyl ethyl cellulose, ethyl propyl methyl cellulose, ethyl propyl,

). The viscosity of the composition is preferably greater than 10 cps. In certain embodiments, the viscosity may also be in the range of 1cps to 10 cps.

In one embodiment, a method of making a composition is disclosed. The method involves mixing the disclosed ingredients in an aqueous carrier to increase the concentration under constant mixing (low shear) conditions until all water-miscible/water-soluble ingredients are uniformly dissolved/dispersed within the carrier. In embodiments involving oil soluble ingredients, a separate oil phase may be prepared (at 30 ℃ to 70 ℃) and then added to the aqueous phase under vigorous stirring conditions (depending on the stability of the ingredients) at 30 ℃ to 70 ℃ until a uniform dispersion is formed.

Eyelid cleanser compositions are typically applied to the surface of the eyelid and surrounding area in the form of a spray, mist, foam, or gel. In certain embodiments, the composition may be administered for a time/frequency specified by a physician. After use, the composition may be left on the surface of the eyelid or surrounding area, or may be wiped off. Whenever the composition is used as a wipe formulation, a less sensitive nonwoven hydrophilic material is recommended to achieve the best results. The composition can be formulated as a residue-free dosage form. The composition has to be applied to open wounds, scars, or visible signs of inflammation, eczema and allergic skin rash. In appearance, the composition may be transparent to translucent, colorless to yellowish.

The eyelid cleanser composition may be contained and dispensed from a suitable container/dispenser. In certain embodiments, the container is a pump dispenser configured to contain and deliver an eyelid cleanser composition as a pre-foamed foam. The eyelid cleanser composition may be selected from the group consisting of: solutions, foams, gels, sprays, lotions, suspensions, emulsions, microemulsions, ointments, and combinations thereof. In certain embodiments, the composition may be biphasic, i.e., have two distinct separate layers within a container that must be shaken prior to application.

In certain embodiments, the eyelid cleanser kit may include one or more fabric pads or wipes impregnated/pre-moistened with a clinically effective amount of the eyelid cleanser composition. The term "pad" refers to a thick piece of fabric that is capable of holding or absorbing the eyelid cleanser composition. For example, the fabric may be a lint-free fabric, such as rayon or another suitable material. In certain embodiments, the fabric pad may be a cotton pad. The pad may be a single use disposable pad. The kit may also include between 1 and 100 pads. The pads may be individually sealed or may be wrapped in any suitable packaging.

In certain embodiments, the kit may include one or more disposable dry pads. Then, a desired amount of the eyelid cleanser composition may be applied to the dry pad prior to cleansing the eyelid with the dry pad. In another embodiment, the kit may include a swab or another suitable applicator/system saturated with the desired amount of eyelid cleanser composition.

It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only.

Claims

1. An eyelid cleanser composition comprising:

(a) hypohalous acid;

(b) one or more surfactants having an HLB value of from 5 to 18; and

(c) an aqueous carrier comprising:

(i) one or more tonicity adjusting agents;

(ii) one or more osmolytes for regulating the osmotic pressure of the composition; and

(iii) one or more pH modifying agents for adjusting the pH of the composition to between about 4.5 to about 8.0.

2. The eyelid cleanser composition of claim 1, wherein the hypohalous acid is hypochlorous acid, and wherein composition comprises from 10ppm to 1000ppm hypochlorous acid.

3. The eyelid cleanser composition of claim 1, wherein the hypohalous acid is hypochlorous acid, and wherein composition comprises 50ppm to 300ppm hypochlorous acid.

4. The eyelid cleanser composition of claim 1, wherein the one or more surfactants have an HLB value of 10-18.

5. The eyelid cleanser composition of claim 1, wherein the composition comprises a combination of surfactants, wherein the first surfactant has an HLB value of 10 to 18 and the second surfactant has an HLB value of 5-10.

6. The eyelid cleanser composition of claim 1, wherein the one or more surfactants are selected from the group consisting of: nonionic surfactants and amphoteric surfactants.

7. The eyelid cleanser composition of claim 6, wherein the one or more surfactants are selected from the group consisting of: sorbitan, sorbitan monolaurate, polyoxyethylene or polyethylene glycol (PEG) modified molecules such as PEG-modified surfactants, PEG-modified phospholipids, PEG-modified sugars, amine oxides, block copolymers, and mixtures thereof.

8. The eyelid cleanser composition of claim 1, wherein the total concentration of the one or more surfactants in the composition ranges from 0.01% w/w to 20% w/w.

9. The eyelid cleanser composition of claim 8, wherein the total concentration of the one or more surfactants in the composition ranges from 0.01% w/w to 5% w/w.

10. The eyelid cleanser composition of claim 1, wherein the tonicity adjusting agent is selected from the group consisting of: sodium chloride, potassium chloride, calcium chloride, magnesium chloride, sodium lactate, potassium lactate, calcium lactate, and mixtures thereof.

11. The eyelid cleanser composition of claim 1, wherein the one or more osmolality adjusting agents are configured to adjust the osmolality of the composition from about 100mOsm/kg to about 500 mOsm/kg.

12. The eyelid cleanser composition of claim 1, wherein the one or more osmolality adjusting agents are selected from the group consisting of: sugar, glycerol, propylene glycol and mixtures thereof.

13. The eyelid cleanser composition of claim 1, wherein the composition is in the form of a foam, liquid, spray, mist, gel, or lotion.

14. The eyelid cleanser composition of claim 1, further comprising a foam stabilizer.

15. The eyelid cleanser composition of claim 14, wherein the foam stabilizing agent is a methyl glucose polyethylene glycol diester and a fatty acid.

16. The eyelid cleanser composition of claim 1, further comprising 0.01% w/w to 5% w/w of one or more ingredients selected from the group consisting of: propylene glycol, glycerin, liquid polyols, nut oils and derivatives, flower extracts, fruit extracts, sodium alginate, hyaluronic acid, diglycerides, triglycerides, PEG-75 lanolin, mineral oil, silicone oil and mixtures thereof.

17. The eyelid cleanser composition of claim 1, further comprising 0.01% w/w to 5% w/w of one or more ingredients selected from the group consisting of: antioxidants, anti-irritants, coolants, viscosity modifiers, and mixtures thereof.

18. A kit for maintaining eyelid hygiene, wherein the kit consists essentially of an applicator and the eyelid cleanser composition of claim 1.

19. The kit of claim 18, wherein the applicator comprises a low-sensitivity nonwoven hydrophilic material.

20. A kit for maintaining eyelid hygiene, wherein the kit consists essentially of an applicator pre-moistened with a clinically effective amount of the eyelid cleanser composition of claim 1.

21. A kit for maintaining eyelid hygiene according to claim 20, wherein the applicator comprises one or more fabric pads, wherein each pad is packaged individually in a sealable package.

22. A method for managing eyelid care comprising applying an effective amount of the eyelid cleanser composition of claim 1 to the eyelid and the area around the eyelid.